Comparative effects of halothane, isoflurane, and sevoflurane on the liver with hepatic artery ligation in the beagle.

Recently, there has been increasing interest in the alterations in splanchnic and hepatic circulation and preservation of hepatic oxygenation and function during anesthesia and surgery. However, the effects of volatile anesthetics under a condition of marginal hepatic oxygen supply are not well understood. Using a crossover design, we therefore studied the effects of equianesthetic concentrations (1.5 MAC) of halothane, isoflurane, and sevoflurane on hepatic oxygenation and function in nine beagles in which the hepatic artery had been ligated. Portal blood flow was measured by an electro-magnetic flow meter. Hepatic function was assessed by indocyanine green elimination kinetics. While cardiac output and mean arterial pressure were greater during halothane anesthesia than during isoflurane and sevoflurane anesthesia, portal blood flow and hepatic oxygen supply were significantly less during halothane and sevoflurane anesthesia than during isoflurane anesthesia. With regard to hepatic oxygen uptake, there was a significant difference between halothane (2.7 +/- 1.2 ml.min-1 x 100 g-1) and sevoflurane (3.7 +/- 2.0 ml.min-1 x 100 g-1; P less than 0.05). Consequently, the hepatic oxygen supply/uptake ratio and the hemoglobin oxygen saturation and oxygen partial pressure in hepatic venous blood during sevoflurane anesthesia were significantly less than they were with the other anesthetics. Indocyanine green clearance was better preserved during sevoflurane anesthesia (39.7 +/- 12.0 ml.min-1) than during halothane anesthesia (30.9 +/- 8.4 ml.min-1; P less than 0.05). We conclude that sevoflurane is accompanied by a smaller oxygen supply/uptake ratio than is halothane and isoflurane, while it preserves hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic oxygen supply and consumption in rats exposed to thiopental, halothane, enflurane, and isoflurane in the presence of hypoxia

Hepatic oxygen supply and uptake were assessed in phenobarbital-pretreated male Sprague-Dawley rats receiving subanesthetic doses of thiopental, halothane, enflurane, or isoflurane combined with hypoxia (approximately 0.5 MAC and 12% oxygen) for the purpose of evaluating the role of these combinations in hepatic blood flow alterations and the concomitant hepatic oxygen supply and uptake. Hepatic blood flow was measured using microspheres; hepatic oxygen supply and consumption was calculated from measured hepatic blood flow and oxygen content in hepatic arterial, portal venous, and hepatic venous blood. In all anesthetic groups, total hepatic blood flow did not change from the control value. Oxygen supply to the liver was decreased from air control values in all anesthetic groups, but there were no significant differences among anesthetic groups. Hepatic oxygen consumption was significantly lower in animals exposed to halothane and isoflurane versus air controls, whereas it was not significantly decreased in animals receiving thiopental or enflurane. The hepatic oxygen supply/consumption ratio was higher in the air control and the isoflurane groups than in other groups; however, no significant differences in this ratio were observed among the thiopental, halothane, and enflurane groups. Oxygen content in hepatic venous blood correlated well with hepatic oxygen supply/consumption ratio in all five groups. These results show that, during exposure to mild hypoxia, a sub-MAC dose of isoflurane maintains the relationship of hepatic oxygen supply to uptake better than thiopental, halothane, or enflurane. However, a subanesthetic dose of halothane did not aggravate liver hypoxia specifically, compared with thiopental or enflurane.     

Effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in normovolemic and hypovolemic cirrhotic rats

The effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in cirrhotic rats that were either normovolemic or hypovolemic following hemorrhage were characterized. Rats received at random either ketamine (30 mg/kg iv, 1.5 mg.kg-1.min-1 iv), halothane, enflurane, or isoflurane (1 MAC). Conscious rats were considered the control group. Four weeks before hemodynamic studies bile duct ligation was performed in all rats to induce cirrhosis. Hemodynamic measurements were performed using the radioactive microsphere method 1 h after the onset of anesthesia and 30 min after hemorrhage. Anesthetized rat lungs were mechanically ventilated with room air. Before hemorrhage cardiac index was higher in conscious rats and in rats receiving isoflurane than in the other groups (P less than 0.001). Hepatic arterial blood flow was similar in conscious rats and in those receiving isoflurane or halothane and was higher than in those receiving ketamine or enflurane. The lowest splanchnic and portal venous tributary blood flows were observed in rats receiving enflurane. After hemorrhage cardiac index was significantly less than before hemorrhage in all groups, except in rats receiving enflurane. After hemorrhage portal venous tributary blood flow decreased significantly in all groups except in enflurane group. During halothane and enflurane anesthesia hepatic arterial blood flow and hepatic arterial fraction of cardiac output decreased (P less than 0.01) and they were maintained in the other groups. After hemorrhage hepatic arterial fraction of cardiac output in conscious rats was higher than in those receiving ketamine, halothane, or enflurane (P less than 0.05) and was similar to those receiving isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of enflurane and isoflurane on hepatic and renal circulations in chronically instrumented dogs

Seven dogs were chronically instrumented for measurements of mean aortic blood pressure and cardiac output and for simultaneous measurements of hepatic, portal, and renal blood flows. Each animal was studied on two separate occasions, awake and during 1.2, 1.4, 1.75, and 2.0 MAC isoflurane and enflurane. Both anesthetics induced tachycardia; to a greater degree than isoflurane, enflurane lowered mean aortic blood pressure in a dose-dependent manner (-37, -45, -48, and -62% vs. -19, -25, -41, and -44%, respectively) and cardiac output (-20, -26, -41, and -48% vs. -3, -5, -11, and -15%, respectively). With isoflurane, cardiac output decreased only at 1.75 and 2.0 MAC, and portal blood flow did not change significantly, whereas hepatic arterial blood flow increased at 1.75 and 2 MAC (by 28 and 33%, respectively). With enflurane, no significant changes were recorded in hepatic arterial blood flow, whereas portal blood flow decreased in a dose-dependent manner. Except at 2 MAC, hepatic circulation did not differ between anesthetics. Likewise, neither anesthetic significantly changed renal blood flow, except for enflurane at 2.0 MAC, which was associated with a 35% reduction. Both anesthetics led to similar systemic, hepatic, and renal vasodilations. Our data suggest that high concentrations of enflurane are associated with decreases in portal, total hepatic, and renal blood flows, most likely as a result of an anesthetic-induced cardiac depression.     

The comparative cardiovascular effects of sevoflurane with halothane and isoflurane

Using closed chest dogs, the cardiovascular effects of sevoflurane were compared with those of halothane and isoflurane in equipotent doses of 1.0, 1.5, 2.0, 2.5 and 3.0 MAC. They were evaluated by the changes of arterial blood pressure, central venous pressure, pulmonary artery pressure, maximum rate of left ventricular pressure rise (LV dp/dt), cardiac output and coronary sinus blood flow. The suppression of left cardiac function by sevoflurane was less than that of halothane, but was greater than that of isoflurane. Heart rate, systemic vascular resistance with sevoflurane were slightly lower than that of isoflurance. The coronary sinus blood flows with sevoflurane and isoflurane were significantly (P < 0.05 at 1.0 MAC, P < 0.005 at 2.0 MAC) higher than halothane. There was no significant difference on coronary sinus flow between sevoflurane and isoflurane. The depth of anesthesia could be quickly changed by adjustment of inspired sevoflurane concentration in comparison with the other two anesthetics.(Kazama T, Ikeda K: The comparative cardiovascular effects of sevoflurane with halothane and isoflurane. J Anesth 2: 63–68, 1988)     

EFFECTS OF ENFLURANE AND HALOTHANE ON LIVER BLOOD FLOW AND OXYGEN CONSUMPTION IN THE GREYHOUND

The effect of increasing inspired concentrations of halothane0.5, 1.0, 1.5, 2.0% and cdurane 1.0, 1.5, 2.0, 3.0% on the hepaticcirculation, were investigated in two groups of anasthetizedgreyhounds. Hepatic arterial a d portal venous blood flow weremeasured continuously using electromagnetic flow probes. Meanarterial pressure and cardiac output were monitored throughouteach investigation. At equiptent anaesthetic concentrationsthere were similar and dose-dependcnt decreases in hepatic arterial,portal venous and total liver blood flows in b t h groups. Enfluraneproduced a more marked decrease in mean arterial pressure thanhalothane because of a significant decrease in systemic vascularresistance. Hepatic arterial resistance decreased significantlywith enflurane but was unchanged in the group receiving halothane.Nather drug affected hepatic oxygen consumption significandy.     

Effects of sevoflurane and isoflurane on hepatic circulation in the chronically instrumented dog.

To compare the effects of sevoflurane and isoflurane on hepatic circulation, eighteen dogs were chronically instrumented for measurements of mean aortic blood pressure and cardiac output and for simultaneous measurements of hepatic and portal blood flows. Each animal was studied while awake and during 1.2 and 2 MAC of either isoflurane or sevoflurane. Both anesthetics induced tachycardia and a dose-dependent decrease in mean aortic blood pressure (isoflurane -27% and -39%; sevoflurane -22% and -37%). Cardiac output decreased only at the highest concentration (isoflurane -10%; sevoflurane -21%). During sevoflurane, portal blood flow decreased at both 1.2 and 2 MAC (-14 and -33%, respectively), whereas an increase in hepatic arterial blood flow was recorded at 2 MAC (+33%). During isoflurane, the only significant change was a decrease in portal blood flow (-16%) at 1.2 MAC. Neither anesthetic significantly changed renal blood flow. Therefore, both anesthetics led to similar systemic and hepatic vasodilation.     

Blood flow and tissue oxygen pressures of liver and pancreas in rats: effects of volatile anesthetics and of hemorrhage.

The object of this investigation was to compare the effects of volatile anesthetics and of hemorrhage at comparable arterial blood pressures on splanchnic blood flow (radioactive microspheres) and tissue oxygenation of the liver and pancreas (surface PO2 [PSO2] electrodes). In contrast to earlier studies, we did not use identical minimum alveolar anesthetic concentration multiples as a reference to compare volatile anesthetics; rather, we used the splanchnic perfusion pressure. Under general anesthesia (intravenous chloralose) and controlled ventilation, 12 Sprague-Dawley rats underwent laparotomy to allow access to abdominal organs. Mean arterial pressure was decreased from 84 +/- 3 mm Hg (mean +/- SEM) at control to 50 mm Hg by 1.0 +/- 0.1 vol% halothane, 2.2 +/- 0.2 vol% enflurane, and 2.3 +/- 0.1 vol% isoflurane in a randomized sequence. For hemorrhagic hypotension, blood was withdrawn gradually until a mean arterial pressure of 50 mm Hg was attained. Volatile anesthetics and hemorrhage reduced cardiac output, and hepatic arterial, portal venous, and total hepatic blood flows by comparable degrees. Mean hepatic PSO2 decreased significantly from 30.7 +/- 2.6 mm Hg at control to 17.4 +/- 2 and 17.5 +/- 2 mm Hg during enflurane and isoflurane (each P less than 0.05) anesthesia, respectively. The decrease to 11.5 +/- 2.5 mm Hg was more pronounced during halothane anesthesia. Hemorrhagic hypotension was associated with the lowest hepatic PSO2 (3.4 +/- 1.3 mm Hg) and the highest number of hypoxic (0-5 mm Hg 86%) and anoxic PSO2 values (0 mm Hg 46%). Pancreatic blood flow and oxygenation remained unchanged from control during halothane and enflurane administration, whereas isoflurane increased both variables. Hemorrhagic hypotension slightly reduced pancreatic flow (-8%) but significantly decreased PSO2 from 58 +/- 5 mm Hg at control to 36 +/- 3 mm Hg, with 7% of all measured values in the hypoxic range. Thus, volatile anesthetics preserved pancreatic but not hepatic blood flow and tissue oxygenation in this rat model. Despite comparable effects on perfusion, the PSO2 of the liver and pancreas was the least during hemorrhagic hypotension compared to that with the anesthetics. Because the volative anesthetic-induced hypotension has such a different effect on splanchnic tissue oxygenation compared with hemorrhagic-induced hypotension, the authors conclude that the method of inducing hypotension may have different effects on oxygenation of various tissues.     

Hepatolobectomy-induced depression of hepatic circulation and metabolism in the dog is counteracted by isoflurane, but not by halothane

BACKGROUND: The effects of isoflurane and halothane anesthesia on hepatic circulation and oxygen metabolism during hepatolobectomy were investigated in the dog, in an attempt to assess which of the anesthetics was the better one for hepatic resection. METHODS: Mongrel dogs (n=24) were divided into two groups and accordingly anesthetized with isoflurane (n=12) or halothane (n = 12). Each test anesthetic was administered in air. Electromagnetic flowmeters were used to measure hepatic arterial and portal venous blood flows 1) before the inhalation of each anesthetic (baseline); 2) 1 h inhalation of 1.5 MAC (minimum alveolar concentration) of each anesthetic; and 3) 1 h after hepatolobectomy with each anesthesia. Measurements of systemic hemodynamics, blood gas tensions, and the arterial ketone body ratio were made at the same time. RESULTS: Isoflurane maintained portal venous, hepatic arterial and total hepatic blood flows better than halothane anesthesia before and after hepatolobectomy. With halothane anesthesia, hepatolobectomy decreased prominently hepatic arterial blood flow. Hepatic arterial and mesenteric vascular resistance increased in the halothane group, but remained constant in the isoflurane group after hepatolobectomy. Hepatic oxygen delivery was significantly suppressed in the halothane group, but did not change in the isoflurane group. No significant difference was found in hepatic oxygen consumption between the two groups, but the arterial ketone body ratio decreased significantly only in the halothane group before and after hepatolobectomy. CONCLUSION: The present data indicate that isoflurane has less adverse effect than halothane anesthesia on hepatic circulation, oxygen delivery and energy charge in hepatolobectomy cases.     

Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs

We investigated the relative effects of 0.5, 1.0, 1.5, 2.0 MAC halothane and enflurane, and concurrent noxious stimulus on hepatic blood flow and oxygen consumption in 14 mongrel dogs randomly divided into groups of seven each. Hepatic arterial and portal venous blood flow (HABF and PVBF, respectively) were measured continuously using ultrasonic transit time flow meter. Mean arterial blood pressure (MAP), cardiac index (CI), hepatic oxygen supply, and hepatic oxygen consumption (H _{O 2}) were measured. Halothane significantly deceased HABF, but not PVBF in a dose dependent manner. Enflurane did not affect HABF and PVBF significantly. MAP and CI decreased in both groups, with halothane producing more marked decreases than enflurane. H _{O 2} did not change with enflurane, but did with halothane, producing significant differences, with halothane being greater at 1.5, 2.0 MAC. A noxious stimulus only caused minor change in blood flow. The results suggest that liver blood flow and oxygen consumption are affected differently by halothane and enflurane and that halothane has a stronger tendency to cause an imbalance between liver oxygen supply and consumption than dose enflurane.(Masaki E, Yasuda N, Tanifuji Y et al.: Effect of halothane and enflurane on hepatic blood flow and oxygen consumption in dogs. J Anesth 3: 118–122, 1989)     

Preservation of the Ratio of Cerebral Blood Flow/Metabolic Rate for Oxygen during Prolonged Anesthesia with Isoflurane, Sevoflurane, and Halothane in Humans

Background: In several animal studies, an increase in cerebral blood flow (CBF) produced by volatile anesthetics has been reported to resolve over time during prolonged anesthesia. It is important to investigate whether this time-dependent change of CBF takes place in humans, especially in clinical situations where surgery is ongoing under anesthesia. In this study, to evaluate the effect of prolonged exposure to volatile anesthetics (isoflurane, sevoflurane, and halothane), the CBF equivalent (CBF divided by cerebral metabolic rate for oxygen (CMRO2)) was determined every 20 min during anesthesia lasting more than 4 h in patients.

Methods: Twenty-four surgical patients were assigned to three groups at random to receive isoflurane, sevoflurane, or halothane (8 patients each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 MAC before surgery and then 1.5 MAC for the 3 h of surgical procedure. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 60 mmHg, using phenylephrine infusion, if necessary. CBF equivalent was calculated every 20 min as the reciprocal of arterial-jugular venous oxygen content difference.

Results: CBF equivalent at 0.5 MAC of isoflurane, halothane, and sevoflurane was 21+/-4, 20+/-3, and 21+/-5 ml blood/ml oxygen, respectively. All three examined volatile anesthetics significantly (P < 0.01) increased CBF equivalent in a dose-dependent manner (0.5, 1.0, 1.5 MAC). At 1.5 MAC, the increase of CBF equivalent with all anesthetics was maintained increased with minimal fluctuation for 3 h. The mean value of CBF equivalent at 1.5 MAC in the isoflurane group (45+/-8) was significantly (P < 0.01) greater than those in the halothane (32+/-8) and sevoflurane (31+/-8) groups. Electroencephalogram was found to be relatively unchanged during observation periods at 1.5 MAC.     

Differential effects of halothane,enflurane, isoflurane,and sevoflurane on the hemodynamics and metabolism in the perfused rat liver in fasted rats

The effects of volatile anesthetics on hepatic hemodynamics and metabolism were studied using isolated liver perfusion. The liver was isolated from overnight-fasted male Sprague-Dawley rats and placed in a recirculating perfusion-aeration system. The liver was perfused through the portal vein at a constant pressure of 12 cmH₂O. Four volatile anesthetics, halothane, enflurane, isoflurane, and sevoflurane, were administered at concentrations identical to 1 and 2 times the minimal alveolar concentration (MAC). All the anesthetics maintained hepatic flow and decreased hepatic oxygen consumption. Among the anesthetics tested, isoflurane produced the largest decrease in hepatic oxygen consumption. At 2 MAC, the percent decrease in oxygen consumption by isoflurane was significantly greater than that by halothane. The increase in lactate concentration in the recirculating perfusate was significantly enhanced by the volatile anesthetics, and the enhancement was less remarkable in the isofluranetreated group than in the enflurane-or sevoflurane-treated groups. These results indicate that volatile anesthetics alter hepatic carbohydrate metabolism but maintain hepatic blood flow when the perfusion pressure is kept constant. Isoflurane exerts exceptional influence on hepatic oxygen consumption and lactate production, and may be preferable for operations that limit the oxygen supply to the liver.     

Blood Flow Velocity of Middle Cerebral Artery during Prolonged Anesthesia with Halothane, Isoflurane, and Sevoflurane in Humans

Background: It is not clear whether the increase of cerebral blood flow (CBF) produced by volatile anesthetics is maintained during prolonged anesthesia. In a previous study, the authors found that CBF equivalent, an index of flow-metabolism relationship, was stable over 3 h, suggesting no decay over time in CBF for 3 h during volatile anesthesia in humans. However, it may be possible that CBF changes in a parallel fashion to functional metabolic changes. In this study, to estimate the response of CBF to three volatile anesthetics, the authors used transcranial Doppler (TCD) ultrasonography to measure time-averaged mean velocity in the middle cerebral artery (Vmca).

Methods: Twenty-four surgical patients were randomly assigned to three groups to receive halothane, isoflurane, or sevoflurane (eight patients, each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5, 1.0, and 1.5 MAC before surgery and then at 1.5 MAC during surgery, which lasted more than 3 h. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 70 mmHg, using phenylephrine infusion, if necessary. TCD recordings of the Vmca were performed continuously.

Results: Vmca at 0.5 MAC of halothane, isoflurane, and sevoflurane was 49 +/- 19, 57 +/- 8, and 48 +/- 13 cm/s, respectively. Halothane significantly (P < 0.01) increased Vmca in a dose-dependent manner (0.5, 1.0, 1.5 MAC), whereas isoflurane and sevoflurane produced no significant dose-related changes. At 1.5 MAC for 3 h, Vmca changed significantly (P < 0.05) for the time trends, but it did not exhibit decay over time with all drugs. During burst suppression, observed electroencephalographically (EEG) on patients during isoflurane and sevoflurane anesthesia, the onset of a burst increased Vmca (approximately 5-30 cm/s), which was maintained for the duration of the burst.     

Hemodynamic and organ blood flow responses to halothane and sevoflurane anesthesia during spontaneous ventilation.

This study compared systemic hemodynamic and organ blood flow responses to equipotent concentrations of halothane and sevoflurane during spontaneous ventilation in the rat. The MAC values for halothane and sevoflurane were determined. Cardiac output and organ blood flows were measured using radiolabeled microspheres. Measurements were obtained in awake rats (control values) and at 1.0 MAC halothane or sevoflurane. The MAC values (mean +/- SEM) for halothane and sevoflurane were 1.10% +/- 0.05% and 2.40% +/- 0.05%, respectively. The PaCO2 increased to a similar extent in both groups compared with control values. During halothane anesthesia, heart rate decreased by 12% (P < 0.01), cardiac index by 26% (P < 0.01), and mean arterial blood pressure by 18% (P < 0.01) compared with control values. Stroke volume index and systemic vascular resistance did not change. During sevoflurane anesthesia, hemodynamic variables remained unchanged compared with control values. Coronary blood flow decreased by 21% (P < 0.01) and renal blood flow by 18% (P < 0.01) at 1.0 MAC halothane, whereas both remained unchanged at 1.0 MAC sevoflurane. Cerebral blood flow increased to a greater extent with halothane (63%; P < 0.01) than with sevoflurane (35%; P < 0.05). During halothane anesthesia, hepatic arterial blood flow increased by 48% (P < 0.01), whereas portal tributary blood flow decreased by 28% (P < 0.01). During sevoflurane anesthesia, hepatic arterial blood flow increased by 70% (P < 0.01) without a concomitant reduction in portal tributary blood flow. Total liver blood flow decreased only with halothane (16%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic circulation during surgical stress and anesthesia with halothane, isoflurane, or fentanyl

Hepatic blood flow and the oxygen supply/uptake relation were studied in 19 miniature pigs using labeled microspheres. Changes in hepatic arterial blood flow and portal blood flow, as well as total hepatic blood flow during halothane anesthesia were more closely associated with changes in mean arterial pressure (MAP) and cardiac output than during anesthesia with isoflurane or fentanyl. Halothane or isoflurane administered in concentrations that decreased MAP by approximately 30% were accompanied by decreases in hepatic oxygen delivery (DO2th) averaging 46% during halothane and 31% during isoflurane anesthesia and parallel decreases in hepatic blood flow. In concentrations that decreased MAP by 50%, halothane and isoflurane decreased DO2th 61 and 37%, respectively. DO2th was maintained (statistically insignificant, 23% increase) during both doses of fentanyl administered (20 micrograms/kg followed by 0.17 microgram . kg-1 . min-1, and 50 micrograms/kg followed by 0.42 microgram . kg-1 . min-1). Hepatic oxygen uptake increased 50% during fentanyl and was maintained at baseline levels during both doses of halothane and isoflurane anesthesia. Oxygen content in hepatic venous blood was maintained at baseline levels during fentanyl and isoflurane administration and was decreased by both concentrations of halothane anesthesia. The hepatic oxygen supply demand ratio was maintained at baseline levels after both doses of fentanyl and during isoflurane administered in a concentration that decreased blood pressure 30%; the ratio decreased during isoflurane administered in a concentration decreasing blood pressure by 50% and during both doses of halothane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrabiliary pressure changes produced by inhalational anesthetics in dogs]

The common bile duct pressure was studied in dogs under inhalation of 1.0 MAC and 2.0 MAC of halothane, enflurane, isoflurane or sevoflurane. A double lumen catheter was inserted into the common bile duct through the cholecystic duct for the measurement of intraductal pressure in the choledochoduodenal junction. The intra-bile-ductal pressure (IBP) was measured with constant rate infusion methods every 10 minutes for one hour. After obtaining control IBP measurements, 44 dogs received randomly either 1.0 MAC (n = 6 in each group) or 2.0 MAC (n = 5 in each group) of each four inhalational anesthetics, through a non-rebreathing system. The decreases in IBP produced by 1.0 MAC concentrations of four inhalation anesthetics were not statistically significant although there was a decline from control measurements obtained for each group. The elevations of IBP following 2.0 MAC halothane, isoflurane or sevoflurane were significantly depressed and were 38.3 +/- 21.2, 67.5 +/- 23.8, 63.7 +/- 23.7 (%, mean +/- SD) of the control levels, respectively. However, 2.0 MAC enflurane produced no significant decrease in IBP.     

Effects of halothane, enflurane, and isoflurane on coronary blood flow autoregulation and coronary vascular reserve in the canine heart

To investigate the effects of volatile anesthetics on coronary blood flow (CBF) autoregulation and coronary vascular reserve, studies were performed on chronically instrumented dogs, awake and during the administration of 1.0 MAC halothane, enflurane, and isoflurane. Coronary pressure-flow plots were generated by measuring left anterior descending coronary artery blood flow while varying coronary inflow pressure with a hydraulic occluder. Autoregulation was quantitated by two measures: the slope of the horizontal "autoregulated" portion of the pressure-flow relationship and the autoregulation index (ArI) of Norris. Slope values (ml.min-1.mmHg-1 +/- SD) were: awake, 0.243 +/- 0.043; halothane, 0.414 +/- 0.044; enflurane, 0.587 +/- 0.187; and isoflurane, 0.795 +/- 0.246. The increase in slope was statistically significant only for halothane and isoflurane (P less than .05). The ArI approaches 1.0 when autoregulation is perfect, and approaches zero or is a negative number when autoregulation is absent. The authors found ArI values of: awake, 0.55; halothane, -0.08; enflurane, -0.01; isoflurane, -0.02. These values indicate good autoregulation while awake, but impaired autoregulation with all three anesthetics (P less than .05). Coronary vascular reserve was calculated, at a diastolic coronary pressure of 40 mmHg, as the difference between resting flow and flow during maximal coronary vasodilation induced by intracoronary adenosine. Coronary vascular reserve, maximal coronary conductance, and coronary zero-flow pressure were not significantly altered by these anesthetics. The authors conclude that 1.0 MAC enflurane, halothane, and isoflurane mildly disrupt CBF autoregulation, increasing CBF out of proportion to myocardial demands. Under the conditions of this study, these anesthetics do not affect maximal CBF or coronary vascular reserve.     

Comparison of the effects of sevoflurane and isoflurane anesthesia on the maternal-fetal unit in sheep

Purpose  The aim of this study was to determine the hemodynamic and blood gas effects of inhalational anesthetics on the maternal-fetal sheep unit. The principal hypothesis, tested in chronically instrumented near-term pregnant ewes, was that sevoflurane anesthesia may be safe and useful for the mother and fetus during pregnancy, compared with isoflurane. Methods  Six chronically instrumented pregnant and 3 nonpregnant ewes were tested repeatedly to establish the minimum alveolar concentration (MAC) for sevoflurane and isoflurane to be used in the hemodynamic and blood gas studies. Progressively increasing concentrations of sevoflurane or isoflurane in oxygen were administered to 12 pregnant ewes. Uterine blood flow, maternal and fetal heart rates, blood pressure, arterial blood gases, and intra-amniotic pressure were subsequently measured. Results  The MAC of sevoflurane was 1.52 ± 0.1 15% and 1.92 ± 0.17% in pregnant and nonpregnant ewes, respectively; while the MAC of isoflurane in the pregnant and nonpregnant sheep was 1.02 ± 0.12% and 1.42 ± 0.19%, respectively. In both the sevoflurane and isoflurane groups, changes in maternal and fetal blood gases were minimal during exposure to low-dose (0.5–1.0 MAC) inhaled concentrations. Although uterine blood flow was maintained and the fetus remained well oxygenated at higher concentrations of both agents (2.0 MAC of either agent), the agents produced decreases in maternal and fetal arterial pressure. Conclusion  A “low-dose” concentration (0.5–1.0 MAC) of sevoflurane may be safe and useful for both mother and fetus during near-term pregnancy. However, a high concentration (1.5–2.0 MAC) of sevoflurane or isoflurane may induce hemodynamic instability in the mother and fetus when administered.     

CEREBRAL EFFECTS OF SEVOFLURANE IN THE DOG: COMPARISON WITH ISOFLURANE AND ENFLURANE

The cerebral effects of sevoflurane were compared in dogs withthose of enflurane and isoflurane. Initially, the minimum alveolarconcentrations (MAC) of sevoflurane and enflurane were determinedand the electroencephalo-graphic (EEG) responses to increasingdoses of sevoflurane (1.5, 2.0 and 2.5 MAC) or enflurane (1.5and 2.0 MAC) in unparalysed animals were examined. Administrationof sevoflurane was not associated with seizure activity at anyconcentration either during normocapnia (Pa_CO2 5.3 kPa) or hypocapnia(Pa_CO2 2.7 kPa), even in the presence of intense auditory stimuli.All dogs anaesthetized with enflurane demonstrated sustainedEEG and motor evidence of seizure activity induced by auditorystimuli at concentrations of enflurane > 1 MAC, particularlyduring hypocapnia. In a separate group of dogs, the effectsof increasing concentrations of sevoflurane and isoflurane (0.5,1.5 and 2.15 MAC) were compared directly on arterial pressure,cardiac output and heart rate, cerebral blood flow and the cerebralmetabolic rate for oxygen (CMRO₂) using the venous outflow technique.Sevoflurane, in common with isoflurane, had minimal effectson cerebral blood flow at the concentrations studied, but significantlyreduced the CMRO₂ at end-tidal concentrations sufficient toproduce a burst suppression pattern on the EEG (approximately2.15 MAC). Both sevoflurane and isoflurane significantly decreasedarterial pressure in a dose-dependent manner, but neither drugsignificantly altered cardiac output.     

Hepatic circulation and oxygen supply-uptake relationships after hepatic ischemic insult during anesthesia with volatile anesthetics and fentanyl in miniature pigs

The objective of the present study was to quantitate the effects of several anesthetics on hepatic circulation, oxygenation, and function after hepatic ischemic insult and during reperfusion. We examined the effects of different anesthetics on hepatic circulation, oxygenation, and function after hepatic ischemic insult in 28 miniature pigs weighing 20-27 kg. The preparation allowed a stepwise decrease followed by a complete cessation for 1 h of hepatic blood and oxygen supply. Immediately after the unclamping of both vessels supplying the liver and restoration of the hepatic circulation, systemic mean arterial pressure decreased to approximately 75% of preischemic values in animals anesthetized with pentobarbital and fentanyl and to 60% of preischemic values in pigs anesthetized with halothane, enflurane, or isoflurane. Total hepatic blood flow immediately returned to preischemic values without significant difference between the groups. Subsequently, hepatic oxygen delivery returned to 75%-95% of preischemic values. Hepatic oxygen uptake returned to 50%-60% of preischemic values in animals anesthetized with pentobarbital and with volatile anesthetics and up to 80% and then later to baseline values with fentanyl anesthesia. Lactate uptake by the liver returned to preischemic values only in animals given fentanyl or isoflurane but remained at approximately 50% of preischemic values during enflurane and 20%-40% during halothane and pentobarbital anesthesia. Thus, the study indicates that both isoflurane and fentanyl anesthesia provide more protection from ischemic insult than do halothane, enflurane, or pentobarbital anesthesia.